In functional mouse adrenal tumor cells (Y-1) ACTH inhibits cell proliferation with a concomitant stimulation of steroidogenesis in tissue culture. A mutant, in which ACTH inhibits cell proliferation without stimulation of steroidogenesis, has been isolated. These observations suggest that there may be two mechanisms of inhibition of cell proliferation by ACTH. The mechanism(s) of inhibition of cell proliferation will be investigated. The properties of this mutant will be characterized and compared with that of the original cells. The effects of ACTH or cAMP on the cell cycle of these cells will be studied. To study further the relationship between stimulation of steroidogenesis and inhibition of cell proliferation and the role of cAMP in these phenomena, mutants with altered responses to ACTH will be isolated and the properties of these mutants will be investigated. The effects of ACTH treatment on the growth of these tumor cells, transplanted into animals, will be studied. The objective is to study whether or not the same mechanism of inhibition of tumor growth is operable in animals. Tissue culture cell lines of normal and neoplastic adrenocortical cells, whose growth is stimulated by ACTH, will be established. The mechanism by which ACTH stimulates cell proliferation will be investigated.